This invention relates to a new means for diagnosing the existence of or the predisposition to hypertension in a mammal, and more particularly, in a human. By use of the diagnostic process described and claimed herein, in humans it is possible to determine the existence of or predisposition to essential hypertension as opposed to secondary hypertension. The invention includes as a preferred embodiment an electrophoretic process for detecting and identifying specific proteins associated with mammalian hypertension in body fluids which were previously undetected and unidentified.
Hypertension is excessive blood pressure in the arterial system which, if left untreated, leads to disability and premature death. Hypertension is generally divided into two broad categories, essential hypertension and secondary hypertension. Essential hypertension is a familial or genetic form of elevation of blood pressure of unknown cause. Secondary hypertension is hypertension of known organic origin such as that associated with renovascular or renal parenchymal disease. The management for essential hypertension differs from that used for secondary hypertension.
By the diagnostic process disclosed and claimed herein, it will be possible to differentiate whether a patient who has hypertension is suffering from essential hypertension or from secondary hypertension. Further, by the process of the present invention, it will be possible to determine which patients may be predisposed to essential hypertension, although they presently may not have elevated blood pressure.
Hypertension is a disease of epidemic proportion affecting some 60 million people in the United States. Hypertension is a major risk factor in the eventual development of significant atherosclerotic complications, namely, myocardial infarction and stroke. Accordingly, It is very important to be able to diagnose and properly treat hypertension, whether it is essential hypertension or secondary hypertension. In addition, hypertension costs the United States more than 8 billion dollars a year in medical costs, lost productivity and lost wages. A significant amount is spent on cost-ineffective investigations directed to exclude secondary hypertension associated with a variety of causes. However it is only by exclusion of evident causes that diagnosis of essential hypertension can be made. This invention is directed to a definite and cost-effective process for the detection of a biochemical marker or markers of essential hypertension.
This invention has primary use in the clinical management of human patients. However, the treatment of other mammals, such as pets and livestock, is also considered to be within the scope of this invention.
The dividing line based on blood pressure measurements between normotension (normal blood pressure) and hypertension is not clear. While certain guidelines have been proposed, there is no absolute blood pressure above which it can be said that high blood pressure or hypertension exists. This is important in that patients or other mammals who are considered normotensive may in fact be hypertensive, and vice versa. Thus, some patients should be treated for hypertension and others should not when the same blood pressure is exhibited. The present invention will help alleviate the grey area between normotension and mild hypertension. Moreover, even when a patient undoubtedly has hypertension, there is frequently no convenient or certain method for determining whether the hypertension is the disease (essential hypertension) or whether it is caused by another disease (secondary hypertension). Since the managements differ, it is important to know which type of hypertension a patient has. The present invention allows this determination.
The present invention is primarily directed to the detection of proteins associated with hypertension in humans and in mammals generally. The preferred process is the use of high resolution discontinuous sodium dodecyl sulfate (sodium dodecyl sulfate will be abbreviated "SDS" hereinafter) polyacrylamide gel electrophoresis, although other qualitative and quantitative methods for the detection of proteins in body fluids may be used.
SDS polyacrylamide gel electrophoresis is a technique that has been used in analyzing protein components of eukaryotic and prokaryotic preparations. For example, see Laemmli, U. K., Nature 277: 680-685, 1970; Ames, G. F. L., Journal of Biological Chemistry 249: 634-644, 1974; Weingarten, M. D., Lockwood, A. H., Hwo, S. Y. & Kirshner, M. W., Proceedings of the National Academy of Sciences, U.S.A. 72: 1858-1863, 1975; Sloboda, R. D., Dentler, W. C. & Rosenbaum, J. L., Biochemistry 15: 4497-4505, 1976; and Fernandes, P. B., Nardi, R. V. & Franklin, S. G., Analytical Biochemistry 91: 101-114, 1978.
Despite these investigations, it is believed that prior to the present invention no one has considered using an electrophoretic gel process for determining the differences between normotensive and hypertensive mammals or the differences between mammals having essential hypertension and mammals having secondary hypertension. It is believed that this is partly because it is generally accepted that essential hypertension represents high blood pressure without evident cause, so that a specific search for biochemical "markers of disease", such as the proteins detected and identified herein, did not appear relevant. Furthermore, until the inventors discovered the existence of proteins associated with at least a predisposition to hypertension, no one could have conceived of a method of detecting and/or identifying them.
Electrophoretic gel analysis has been used to detect other diseases or pathological problems (see, for example, U.S. Pat. No. 3,607,695 of Schneider, issued Sept. 21, 1971 and U.S. Pat. No. 3,687,833 of Parcells et al, issued Aug. 29, 1972), but the use of gel electrophoresis has not been considered with respect to the determination of factors affecting hypertension.